Novel Allogenic CD19-targeting Chimeric Antigen Receptor γδT Cells Therapy (QH103E) in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
CD19-CAR-γδT cell therapy is a cellular immunotherapy targeting CD19 to perform CAR modification on allogeneic γδT cells. A novel version of the CAR-γδT product by gene editing (QH103E) that has been validated for resistance to alloreactive T cell killing and enhancement of memory efficacy will be used in this study. This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) will be enrolled in the study and receive QH103E product infusion. Phase 1 (n=9 to 12) is dose escalation part, and phase 2 (n=15 to 20) is expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of QH103E in patients with r/r B-cell NHL.
• Age 18-75 (inclusive).
• Patients with histologically confirmed CD19-positive B-cell NHL.
• Relapse after treatment with ≥2 lines systemic therapy for all the B-cell NHL disease types, or refractory disease for aggressive types (DLBCL-NOS, PMBCL, TFL and HGBCL). Relapse disease is defined as disease progression after last regimen. Refractory disease is defined as no CR to first-line therapy:
‣ PD as best response to first-line therapy, or
⁃ SD as best response after at least 4 cycles of first-line therapy (eg,4 cycles of R-CHOP), or
⁃ PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months of therapy. or refractory post-autologous stem cell transplant (ASCT): i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals); ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
• The estimated survival time is over 3 months.
• The Eastern Cooperative Oncology Group (ECOG) score is 0-2.
• According to Lugano response criteria 2014, there should be at least one evaluable tumor focus. Evaluable tumor focus was defined as that with the longest diameter of intranodal focus \> 1.5cm, the longest diameter of extranodal focus \> 1.0cm assessed by computed tomography (CT) or magnetic resonance imaging (MRI).
• Subjects must be willing to undergo either excised or large-needle lymph node or tissue biopsy, or provide formalin-fixed paraffin-embedded (FFPE) tumor tissue block or freshly cut unstained slides.
• Functions of important organs meet the following requirements:
• Echocardiography showed left ventricular ejection fraction ≥50%. Serum creatinine ≤1.5 × upper limit of normal range (ULN) or endogenous creatinine clearance ≥45mL/min (cockcroft-gault formula); Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3 times ULN, Total bilirubin ≤1.5× ULN; Pulmonary function: ≤CTCAE grade1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.
• Blood routine (normal values shall not be obtained with growth factors, and hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions below): hemoglobin (Hgb) ≥80g/L, neutrophil count≥1×10\^9/L, platelet (PLT) ≥75×10\^9/L.
⁃ Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.
⁃ Toxicity from previous antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or to an acceptable level of inclusion/exclusion criteria (other toxicities such as alopecia and vitiligo considered by the investigator to pose no safety risk to the subject).
⁃ No obvious hereditary diseases.
⁃ Able to understand the requirements and matters of the trial, and willing to participate in clinical research as required.
⁃ Informed consent must be signed.